Genes & Development,
Год журнала:
2012,
Номер
26(7), С. 657 - 667
Опубликована: Апрель 1, 2012
The
nuclear
receptor
Rev-erbα
regulates
circadian
rhythm
and
metabolism,
but
its
effects
are
modest
it
has
been
considered
to
be
a
secondary
regulator
of
the
cell-autonomous
clock.
Here
we
report
that
depletion
together
with
closely
related
Rev-erbβ
dramatic
on
clock
as
well
hepatic
lipid
metabolism.
Mouse
embryonic
fibroblasts
were
rendered
arrhythmic
by
both
Rev-erbs.
In
mouse
livers,
mRNA
protein
levels
oscillate
diurnal
pattern
similar
Rev-erbα,
Rev-erbs
recruited
remarkably
set
binding
sites
across
genome,
enriched
near
metabolic
genes.
Depletion
in
liver
synergistically
derepresses
several
genes
control
positive
limb
molecular
Moreover,
deficiency
causes
marked
steatosis,
contrast
relatively
subtle
changes
upon
loss
either
subtype
alone.
These
findings
establish
two
major
regulators
function
displaying
level
collaboration
is
unusual
among
receptors
common
core
proteins,
protecting
organism
from
perturbations
physiology.
Annual Review of Neuroscience,
Год журнала:
2012,
Номер
35(1), С. 445 - 462
Опубликована: Май 20, 2012
The
circadian
system
of
mammals
is
composed
a
hierarchy
oscillators
that
function
at
the
cellular,
tissue,
and
systems
levels.
A
common
molecular
mechanism
underlies
cell-autonomous
oscillator
throughout
body,
yet
this
clock
adapted
to
different
functional
contexts.
In
central
suprachiasmatic
nucleus
(SCN)
hypothalamus,
coupled
population
neuronal
acts
as
master
pacemaker
for
organism
drive
rhythms
in
activity
rest,
feeding,
body
temperature,
hormones.
Coupling
within
SCN
network
confers
robustness
pacemaker,
which
turn
provides
stability
overall
temporal
architecture
organism.
Throughout
majority
cells
clocks
are
intimately
enmeshed
metabolic
pathways.
Thus,
an
emerging
view
adaptive
significance
their
fundamental
role
orchestrating
metabolism.
Science,
Год журнала:
2010,
Номер
330(6009), С. 1349 - 1354
Опубликована: Дек. 2, 2010
Circadian
clocks
align
behavioral
and
biochemical
processes
with
the
day/night
cycle.
Nearly
all
vertebrate
cells
possess
self-sustained
that
couple
endogenous
rhythms
changes
in
cellular
environment.
Genetic
disruption
of
clock
genes
mice
perturbs
metabolic
functions
specific
tissues
at
distinct
phases
sleep/wake
desynchrony,
a
characteristic
shift
work
sleep
humans,
also
leads
to
pathologies.
Here,
we
review
advances
understanding
interrelationship
among
circadian
disruption,
deprivation,
obesity,
diabetes
implications
for
rational
therapeutics
these
conditions.
Physiological Reviews,
Год журнала:
2012,
Номер
92(3), С. 1087 - 1187
Опубликована: Июль 1, 2012
This
review
summarizes
the
brain
mechanisms
controlling
sleep
and
wakefulness.
Wakefulness
promoting
systems
cause
low-voltage,
fast
activity
in
electroencephalogram
(EEG).
Multiple
interacting
neurotransmitter
stem,
hypothalamus,
basal
forebrain
converge
onto
common
effector
thalamus
cortex.
Sleep
results
from
inhibition
of
wake-promoting
by
homeostatic
factors
such
as
adenosine
nitric
oxide
GABAergic
neurons
preoptic
area
resulting
large-amplitude,
slow
EEG
oscillations.
Local,
activity-dependent
modulate
amplitude
frequency
cortical
Non-rapid-eye-movement
(NREM)
conservation
energy
facilitates
memory
consolidation
through
modulation
synaptic
weights.
Rapid-eye-movement
(REM)
interaction
stem
cholinergic,
aminergic,
which
control
glutamatergic
reticular
formation
leading
to
REM
phenomena
muscle
atonia,
REMs,
dreaming,
activation.
Strong
activation
limbic
regions
during
suggests
a
role
regulation
emotion.
Genetic
studies
suggest
that
waking
NREM
are
strongly
conserved
throughout
evolution,
underscoring
their
enormous
importance
for
function.
disruption
interferes
with
normal
restorative
functions
sleep,
disruptions
breathing
cardiovascular
function,
changes
emotional
reactivity,
cognitive
impairments
attention,
memory,
decision
making.
Annual Review of Physiology,
Год журнала:
2010,
Номер
72(1), С. 551 - 577
Опубликована: Фев. 11, 2010
The
suprachiasmatic
nucleus
(SCN)
is
the
primary
circadian
pacemaker
in
mammals.
Individual
SCN
neurons
dispersed
culture
can
generate
independent
oscillations
of
clock
gene
expression
and
neuronal
firing.
However,
rhythmicity
depends
on
sufficient
membrane
depolarization
levels
intracellular
calcium
cAMP.
In
intact
SCN,
cellular
are
synchronized
reinforced
by
rhythmic
synaptic
input
from
other
cells,
resulting
a
reproducible
topographic
pattern
distinct
phases
amplitudes
specified
circuit
organization.
network
synchronizes
its
component
oscillators,
reinforces
their
oscillations,
responds
to
light
altering
phase
distribution,
increases
robustness
genetic
perturbations,
enhances
precision.
Thus,
even
though
individual
be
cell-autonomous
properties
integral
normal
function
SCN.
Science,
Год журнала:
2009,
Номер
324(5927), С. 651 - 654
Опубликована: Март 20, 2009
The
circadian
clock
is
encoded
by
a
transcription-translation
feedback
loop
that
synchronizes
behavior
and
metabolism
with
the
light-dark
cycle.
Here
we
report
both
rate-limiting
enzyme
in
mammalian
nicotinamide
adenine
dinucleotide
(NAD+)
biosynthesis,
phosphoribosyltransferase
(NAMPT),
levels
of
NAD+
display
oscillations
are
regulated
core
machinery
mice.
Inhibition
NAMPT
promotes
oscillation
gene
Per2
releasing
CLOCK:BMAL1
from
suppression
SIRT1.
In
turn,
transcription
factor
CLOCK
binds
to
up-regulates
Nampt,
thus
completing
involving
NAMPT/NAD+
SIRT1/CLOCK:BMAL1.
Physiological Reviews,
Год журнала:
2010,
Номер
90(3), С. 1063 - 1102
Опубликована: Июль 1, 2010
Mammalian
circadian
rhythms
are
controlled
by
endogenous
biological
oscillators,
including
a
master
clock
located
in
the
hypothalamic
suprachiasmatic
nuclei
(SCN).
Since
period
of
this
oscillation
is
∼24
h,
to
keep
synchrony
with
environment,
need
be
entrained
daily
means
Zeitgeber
(“time
giver”)
signals,
such
as
light-dark
cycle.
Recent
advances
neurophysiology
and
molecular
biology
rhythmicity
allow
better
understanding
synchronization.
In
review
we
cover
several
aspects
mechanisms
for
photic
entrainment
mammalian
rhythms,
retinal
sensitivity
light
novel
photopigments
well
variations
retina
that
contribute
regulation
physiology.
Downstream
from
retina,
examine
retinohypothalamic
communication
through
neurotransmitter
(glutamate,
aspartate,
pituitary
adenylate
cyclase-activating
polypeptide)
interaction
SCN
receptors
resulting
signal
transduction
pathways
neurons,
putative
neuron-glia
interactions.
Finally,
describe
analyze
gene
expression
its
importance
mechanisms,
disorders
or
diseases
related
deficits,
experimental
clinical
treatments.
